This study aimed to investigate the healing effect of a polylactic-co-glycolic acid (PLGA) scaffold containing nanohydroxyapatite (NHA) along with curcumin (CCM), loaded with adipose-derived mesenchymal stem cells (AD-MSCs), on mandibular bone defects. The designed PLGA scaffolds containing NHA were evaluated for their mechanical and structural properties. Forty rats were divided into five groups (n = 8) based on the treatment: Sham, PLGA scaffolds containing NHA, PLGA scaffolds containing NHA + CCM, PLGA scaffolds containing NHA + AD-MSCs, and PLGA scaffolds containing NHA + CCM + AD-MSCs. After 8 weeks' follow-up, mandible bones were isolated for histomorphometry evaluation. Data were analyzed using SPSS version 21, with p-values <0.05 considered statistically significant. SEM evaluation showed that the designed nanocomposite scaffold had 80% porosity. Histomorphometry results indicated a significant difference in osteocyte, osteoblast, bone area, and vascular area parameters in the group treated with scaffolds loaded with AD-MSCs + CCM compared to the other groups (p < 0.05). The PLGA-containing NHA-CCM nanocomposite scaffold demonstrated good porosity and dispersion, suitable for treating bone defects. Rats treated with scaffolds containing AD-MSCs and CCM showed better therapeutic results than the other groups. Further research is needed to evaluate its anti-inflammatory, antioxidant properties, osteogenesis, and therapeutic effects in larger animal models.